We claim:
1. A process for the preparation of solid dispersion comprising Asciminib
hydrochloride (1) with at least one pharmaceutically acceptable excipient,
comprising the steps of:
a) dissolving Asciminib free base (2) in a solvent or mixture of solvents,
b) adding a solution of hydrochloric acid to the solution obtained in step a),
c) optionally, adding second solvent or mixture of solvents to step b),
d) adding at least one pharmaceutically acceptable excipient to the solution
obtained in step-c), and
e) isolating the solid dispersion of Asciminib hydrochloride (1).
wherein, the process involves without isolation of Asciminib hydrochloride (1);
wherein the ratio of Asciminib hydrochloride (1) with at least one
pharmaceutically acceptable excipient ranges from about 1:0.5 to about 1:5
(w/w).
2. A process for the preparation of solid dispersion comprising Asciminib
hydrochloride (1) with at least one pharmaceutically acceptable excipient,
comprising the steps of:
a) dissolving Asciminib free base (2) in a solvent or mixture of solvents,
b) adding at least one pharmaceutically acceptable excipient to the solution
obtained in step-a),
c) isolating the solid dispersion of Asciminib free base,
d) dissolving solid dispersion of Asciminib free base (2) in a solvent or mixture
of solvents
e) adding a solution of hydrochloric acid to step d), and
f) isolating the solid dispersion of Asciminib hydrochloride (1).
wherein, the process involves without isolation of Asciminib hydrochloride (1);
wherein the ratio of Asciminib hydrochloride (1) with at least one
pharmaceutically acceptable excipient ranges from about 1:0.5 to about 1:5
(w/w).
3. The process as claimed in claim 1 to 2, wherein the solution of hydrochloric acid
is selected from but not limited to alcoholic hydrochloric acid, aqueous
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hydrochloric acid, concentrated hydrochloric acid or ethyl acetate hydrochloric
acid.
4. The process as claimed in claim 3, wherein the alcoholic hydrochloric acid is
selected from methanolic hydrochloric acid, ethanolic hydrochloric acid and the
like.
5. A process for the preparation of solid dispersion comprising Asciminib free base
(2) with at least one pharmaceutically acceptable excipient, comprising the steps
of:
a) dissolving Asciminib free base (2) in a solvent or mixture of solvents,
b) adding at least one pharmaceutically acceptable excipient to the solution
obtained in step-a), and
c) isolating the solid dispersion of Asciminib free base (2).
6. A process for the preparation of solid dispersion comprising Asciminib
hydrochloride (1) with hydroxypropyl methylcellulose-E3 (HPMC-E3),
comprising the steps of:
a) dissolving Asciminib free base (2) in methanol,
b) adding methanolic hydrochloric acid to the solution obtained in step a),
c) adding hydroxypropyl methylcellulose-E3 (HPMC-E3) to the solution
obtained in step-b), and
d) isolating the solid dispersion of Asciminib hydrochloride (1).
wherein, the process involves without isolation of Asciminib hydrochloride (1);
wherein the ratio of Asciminib hydrochloride (1) with at least one
pharmaceutically acceptable excipient ranges from about 1:0.8.
7. A process for the preparation of solid dispersion comprising Asciminib
hydrochloride (1) with at least one pharmaceutically acceptable excipient,
comprising the steps of:
a) dissolving Asciminib hydrochloride (1) in a solvent or mixture of solvents,
b) adding at least one pharmaceutically acceptable excipient to the solution
obtained in step-a), and
c) isolating the solid dispersion of Asciminib hydrochloride (1).
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wherein the ratio of Asciminib hydrochloride (1) with at least one
pharmaceutically acceptable excipient ranges from about 1: 0.5 to about 1:5
(w/w).
8. The process as claimed in claim 1 to 7 wherein, the solvent is selected from
alcohol solvents such as methanol, ethanol, 1 -propanol, 2-propanol, 1-butanol,
2-butanol, and the like; chloro solvents such as dichloromethane, 1, 2-
dichloroethane, trichloroethylene, chloroform, carbon tetrachloride, and the like;
polar aprotic solvents such as dimethyl formamide, dimethyl sulfoxide, dimethyl
acetamide and the like; water or its mixture thereof.
9. The process as claimed in claim 1 to 7 wherein, the pharmaceutically acceptable
excipient is selected from but not limited to polyvinylpyrrolidone (povidone or
PVP), polyvinylpolypyrrolidone, Polyvinylpyrrolidone-K-30 (PVP-K-30),
polysorbate, cross linked polyvinyl pyrrolidone (crospovidone), polyethylene
glycol (macrogol or PEG), polyvinyl alcohol, polyvinyl chloride, polyvinyl
acetate, propylene glycol, cellulose, cellulose acetate phthalate (CAP), methyl
cellulose, carboxymethyl cellulose (CMC, its sodium and calcium salts),
carboxymethylethyl cellulose (CMEC), ethyl cellulose, hydroxymethyl
cellulose, ethyl hydroxyethyl cellulose, hydroxyethylcellulose, hydroxypropyl
cellulose (HPC), hydroxypropyl cellulose acetate succinate (HPCAS),
hydroxypropyl beta cyclodextrin (HPβCD), Salcaprozate sodium, sodium
caprylate, Soluplus, hydroxypropyl methyl cellulose (hypromellose or HPMC),
hydroxypropyl methylcellulose acetate succinate (HPMC-AS), hydroxypropyl
methylcellulose-ES (HPMC-ES), hydroxyethyl methyl cellulose succinate
(HEMCS), sulfobutylether-β-cyclodextrin (SBCED), Hydroxypropyl
methylcellulose-E3 (HPMC-E3), hydroxypropyl methylcellulose phthalate
(HPMC-P), hydroxypropyl methylcellulose acetate phthalate, microcrystalline
cellulose (MCC), syloid, eudragit, copovidone, maltodextrin, mannitol or
isomalt.
10. The process as claimed in claim 1 to 7 wherein, isolating the solid dispersion of
Asciminib free base (2) or its hydrochloride (1) involves removal of solvent by
decantation, evaporation under reduced pressure, flash evaporation, vacuum
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drying, concentrating the reaction mixture, atmospheric distillation, distillation
under reduced pressure, distillation by using a rotational distillation device such
as Buchi rotavapor, agitated thin film drying (ATFD), melt extrusion, spray
drying, freeze drying (lyophilization), spray-freeze drying, cooling the clear
solution to lower temperatures to precipitate the solid followed by filtration by
gravity or suction, thin film drying, centrifugation.